Biphenyl → 5-Thiazol-2-yl-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 1038032

반응식

HRID 1038032 반응식
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.CC(C)([O-])C.[Na+].[C:13]([O:17][C:18]([N:20]1[CH2:25][C@@H:24]2[CH2:26][C@H:21]1[CH2:22][NH:23]2)=[O:19])([CH3:16])([CH3:15])[CH3:14].C1(C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.C(OCC)(=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH:24]2[CH2:26][CH:21]1[CH2:22][N:23]2[C:2]1[S:3][CH:4]=[CH:5][N:6]=1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

참가 물질

9

반응물 4

HCID 7095BiphenylHCID 764302-BromothiazoleHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 23676156Sodium t-butoxide

생성물 1

HCID 669396205-Thiazol-2-yl-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester수율 52%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

A mixture of 2-bromothiazole (200 mg, 1.22 mmol), palladium acetate (15 mg, 0.06 mmol), sodium tert-butoxide (217 mg, 2.26 mmol), (S,S) 2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (280 mg, 1.4 mmol) and 2-Di-t-butylphosphino)-biphenyl (37 mg, 0.118 mmol) was stirred in dioxane (10 ml) at 80° C. for overnight. The reaction was cooled, diluted with ethyl acetate (40 ml) and H2O (50 ml). The organic layer was separated, dried (Na2SO4), filtered and solvent evaporated. The residue was purified by chromatography eluting with 5% MeOH/DCM yielding product as a white solid. (180 mg, 52% yield)

후처리

  1. temperatureThe reaction was cooled
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customsolvent evaporated
  6. customThe residue was purified by chromatography
  7. washeluting with 5% MeOH/DCM yielding product as a white solid

출처 및 근거

ORD 기록
ord-5f0d31b3dc66434a9d00699ec56389b2
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546404B2

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